Medical Management of ectopic pregnancy with Methotrexate

Medically Reviewed by:Jackie Ross BSc MB.BS MRCOG& Professor Andrew Horne MB ChB PhD FRCOG FRCP& Professor Colin Duncan BSC(hons), MBChB(hons), MD, FRCOG
Last Reviewed:17/04/2023
Next review date:01/04/2026
Written by: The Ectopic Pregnancy Trust

Do you or someone you know have symptoms?

Around 1 in 80 pregnancies are ectopic in the UK. Find out more about symptoms of an ectopic pregnancy.

Treating an ectopic pregnancy

If you have been diagnosed as having an ectopic pregnancy and are stable, with pulse and blood pressure within normal limits, and there is no vaginal bleeding or severe abdominal pain, and if there are no signs of dizziness or fainting, your doctor will be able to discuss various treatment options with you.

Unfortunately, a number of women have no early symptoms so present for assessment after a time when there are still options available for treatment. If you are bleeding heavily, in severe pain or have signs of dizziness or fainting, your doctor will probably suggest an exploratory surgical operation called a laparoscopy which is done via keyhole surgery to allow them to take a look inside your abdomen to see what might be happening.

New treatment methods are being developed but set out below are the options that you are likely to be currently advised. An ectopic pregnancy can also be treated by Surgical management or Expectant management.

Medical management with methotrexate

The term ‘medical management, when used in relation to ectopic pregnancy, means using a drug called methotrexate. Folate is an essential vitamin needed to help rapidly dividing cells in pregnancy and methotrexate is a powerful drug that works by temporarily interfering with the processing in the body of folate. The drug stops the pregnancy developing any further and it is gradually reabsorbed by the body leaving the Fallopian tube intact.

Methotrexate treatment is most effective in the early pregnancy stages, usually when the pregnancy hormone ‘beta hCG’ (human chorionic gonadotropin) level is below 5000 mIU/mL. The risk of rupture is higher in pregnancies with levels greater than this. However, in interstitial ectopic pregnancy, it is not unusual to try to treat ectopic pregnancy with the drug with higher levels of hCG in the body. With ectopic pregnancy, it is not really the stage of pregnancy (as in the number of weeks gestation), but the size of the ectopic, which can vary over the first few weeks depending on the rate of growth, that is important.

For a more detailed understanding of when methotrexate might be considered, looking at the medical professional’s RCOG Green-top Guideline 21 and the NICE Ectopic Pregnancy and Miscarriage Guidance might be helpful.

The treatment is given by means of an injection, usually given by a single injection into the buttock (the muscle of your bottom), however, if it needs to be administered by any other route, this will be discussed with you. The dose is calculated according to your height and weight. Before the injection, blood tests are done to check liver and kidney function and to ensure that you are not anaemic.

This method has been developed to avoid surgery. However, it does require careful monitoring and follow-up. This means that you will have to attend the hospital regularly for blood tests to monitor your hCG levels until the tests are negative. This can take several weeks, and this will be explained by your doctor. Your hospital will make arrangements for you to have the hormone level checked. Your doctors will usually test your hCG levels on the day the medicine is given, again on day four, and on day seven after the injections.

The hCG level often rises on the day four blood test because the action of methotrexate is not instantaneous, so the cells will have continued to divide for two or three days after the injection was given, and some cells release more hCG when they start to disappear. Your doctors are looking to see a drop in your hCG value of at least 15% between days four and seven. If there has not been a 15% drop, this is when the doctors will consider a second dose of methotrexate or surgery.

A few days after the injection, it is usual to begin to bleed and this bleeding can last between a few days and up to 6 weeks.

Every 3-7 days, beta hCG levels will continue to be monitored to ensure that they are falling appropriately. Most only need single-dose methotrexate injection but in up to a quarter of cases a further injection may be required if serum hCG levels are not decreasing.

Methotrexate is at least as good as surgery in terms of subsequent successful pregnancies. This may be due to the fact that medical treatment is non-invasive, whereas surgery may risk factors like some scarring around the Fallopian tube.

Medical Management downloadable PDF 

Commonly asked questions about medical management with methotrexate

What are the risk factors of methotrexate treatment?

The risk associated with treating being treated medically is that the medicine may not work as the cells of the ectopic pregnancy may continue to divide, which could result in there still being a need for surgery. Success rates do vary depending on the circumstances in which methotrexate is given. Studies report success rates of 65-95%. Success rates tend to be higher with lower serum hCG levels. Your doctor should be able to tell you the success rate of methotrexate in their unit. Doctors can tell if the specialised cells of a pregnancy that produce the hCG hormone are still dividing because the hCG level will continue to rise and not fall. This will be monitored through blood tests.

Occasionally, an ectopic pregnancy can rupture despite low hCG levels. Your hospital should have given you a number to contact for health advice if you feel that anything is changing, or you will have been told to report to the Accident and Emergency (A&E) department. If you have not been told what to do and need to speak to someone ring the hospital department which is treating you or the NHS 111 Service by dialling 111.

Women with ectopic pregnancies in a Fallopian tube who are treated with methotrexate:

  • require a second dose of methotrexate in 14% of cases (14 out of 100 women); and 
  • require surgery in 29% of cases (29 out of 100 women), despite treatment with methotrexate.
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What are the side effects of methotrexate?

The most common side effects of methotrexate are:

  • Cramping abdominal (tummy) pain is the most common side effect, and it usually occurs during the first 2 to 3 days of treatment. Because abdominal pain is also a sign of a ruptured ectopic pregnancy, report any abdominal pain to your health professional;
  • Fatigue – a number of women feel very tired and are shocked by the sheer exhaustion that they encounter during treatment;
  • Vaginal bleeding or spotting;
  • Nausea, vomiting, and indigestion;
  • Light-headedness or dizziness – Again, because this is also a sign of a ruptured ectopic pregnancy, please report it to your health professional;
  • A numb or sore bottom from the injection.

Other rarer side effects from methotrexate treatment for ectopic pregnancy, include:

  • Skin sensitivity to sunlight
  • Inflammation of the membrane covering the eye
  • Sore mouth and throat
  • Temporary hair loss
  • Severe low blood counts (bone marrow suppression)
  • Inflammation of the lung (pneumonitis)
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Is this method of ectopic pregnancy treatment suitable for me?

This method of treatment is more suitable for some than others and is more likely to be successful in the following circumstances:

  • You are in good health
  • Your Fallopian tube has not ruptured
  • Your hCG level is low enough (your hospital will probably have a level above which this method will not be used)
  • There is no significant abdominal bleeding

Because it does not entail an operation, this method has a particular advantage over surgery if:

  • You have other medical problems that may increase the risks of a general anesthetic
  • If you have adhesions in the abdomen or pelvis (as a result of previous surgery or infection)
  • The ectopic pregnancy is situated in the neck of the womb or as the Fallopian tube enters the womb

Treatment of ectopic pregnancy with methotrexate is not appropriate if you suffer from any of the following conditions:

  • An ongoing infection
  • Severe anemia or shortage of other blood cells
  • Kidney problems
  • Liver problems
  • Active infection
  • Peptic ulcer or ulcerative colitis
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What can I do to help the treatment work?

You should stop taking any vitamins, minerals, or other medicines unless you have been told by the doctors treating you to continue with them, as some interfere with the effects of methotrexate. It is particularly important that you do not take any folic acid supplements and avoid foods enriched with folic acid until your doctors are sure that the drug has worked and hCG hormone level has returned to non-pregnant.

You should not do any heavy lifting or housework until the hCG levels are dropping consistently and should only undertake gentle exercise, such as walking, until the hCG (pregnancy hormone) is at non-pregnant level.

You should avoid sexual intercourse until your hCG is down to non-pregnant level.

Most people take time off from work initially and do not return to work for at least two weeks while the treatment begins to work.  Our website has information about ectopic pregnancy and the workplace.

In the first week, it is important to avoid pain killers which fall into the NSAID group such as ibuprofen. The preferred painkiller is paracetamol.  

You should refrain from drinking alcohol until hCG has fallen to a non-pregnant level and not drink alcohol for a few weeks after that.

Below are links to further information on physical recovery and emotional recovery after an ectopic pregnancy.

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How long will the treatment take?

This usually takes a few weeks. According to a study, for women with ectopic pregnancies in a Fallopian tube who are treated with methotrexate (with hCG of 1000–5000 IU/L before treatment), it takes an average of 28 days for the ectopic pregnancy to resolve (when medical treatment is successful).

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I'm not being offered methotrexate. What should I do?

Although you may be eligible for methotrexate, the use of methotrexate for treatment of ectopic pregnancies across the UK is still varied. It may be that in one authority they use it and in the next, they do not. The decision ultimately lies with your medical team within the health authority you are under, but you can make your wishes clear and ask to be assessed by a unit that does use methotrexate.

If you would like methotrexate to be considered as an ectopic pregnancy treatment in your case, you are within your rights to ask to be referred to a unit where it is available. You should ask to be referred to a consultant within the Primary Care Trust who can assess your suitability for this kind of treatment or on to another treatment centre.

If you need any help with this, you need to contact the Patient Advice and Liaison Services (PALS) at the hospital where you are being treated. They can help you locate an assessment or new consultant if you need to.

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